Biodegradable microcapsules of pentamidine/poly(L-lactide-co-D,L-lactide) were prepared by solvent evaporation technique using a mixture of organic solvents. The control batch of microcapsules was prepared using dichloromethane. The effect of solvent on the characteristics of pentamidine loaded microcapsules was examined by substituting up to 30% of dichloromethane with acetone, methanol, DMSO, ethyl acetate, and ethanol, respectively. No significant change in the surface morphology was observed when dichloromethane was substituted with 20% or less amount of other solvents. These microcapsules were all porous and spherical. However, the use of 30% DMSO or ethanol, along with dichloromethane, resulted in a mixture of elongated and spherical microcapsules. The efficiency of encapsulation of these two batches was also significantly higher than the other batches of microcapsules. The average particle size of the microcapsules prepared with 30% DMSO (165 μm) was significantly higher than the other batches ( < 80 μm). A substitution of 10-30% dichloromethane with other listed organic solvents also showed a significant difference in the initial drug release. The drug release within the first twenty-four hours varied from 4 to 16%. The use of a second organic solvent, except ethanol, resulted in a significantly higher drug release during the second half of the dissolution study. The drug release continued more than 60 days.